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PDBsum entry 4ilx

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protein ligands metals links
Lyase/lyase inhibitor PDB id
4ilx
Jmol
Contents
Protein chain
257 a.a.
Ligands
GOL ×2
1EZ
DMS
Metals
_ZN
Waters ×261
PDB id:
4ilx
Name: Lyase/lyase inhibitor
Title: Structure of human carbonic anhydrase ii in complex with an sulfonamide inhibitor
Structure: Carbonic anhydrase 2. Chain: a. Synonym: carbonate dehydratase ii, carbonic anhydrasE C, ca carbonic anhydrase ii, ca-ii. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ca2. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.60Å     R-factor:   0.150     R-free:   0.185
Authors: S.Biswas,R.Mckenna
Key ref: S.Biswas et al. (2013). Structural effect of phenyl ring compared to thiadiazole based adamantyl-sulfonamides on carbonic anhydrase inhibition. Bioorg Med Chem, 21, 2314-2318. PubMed id: 23490152 DOI: 10.1016/j.bmc.2013.02.022
Date:
01-Jan-13     Release date:   13-Feb-13    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2
Seq:
Struc:
260 a.a.
257 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.4.2.1.1  - Carbonate dehydratase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: H2CO3 = CO2 + H2O
H(2)CO(3)
= CO(2)
+ H(2)O
      Cofactor: Zinc
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular space   10 terms 
  Biological process     angiotensin-mediated signaling pathway   20 terms 
  Biochemical function     protein binding     5 terms  

 

 
    Added reference    
 
 
DOI no: 10.1016/j.bmc.2013.02.022 Bioorg Med Chem 21:2314-2318 (2013)
PubMed id: 23490152  
 
 
Structural effect of phenyl ring compared to thiadiazole based adamantyl-sulfonamides on carbonic anhydrase inhibition.
S.Biswas, F.Carta, A.Scozzafava, R.McKenna, C.T.Supuran.
 
  ABSTRACT  
 
We investigated the inhibitory activity of sulfonamides incorporating adamantyl moieties against the physiologically relevant human (h) CA (EC 4.2.1.1) isoforms hCA I, II III (cytosolic), IX and XII (transmembrane, tumor-associated). The presence of a benzenesulfonamide instead of an 1,3,4-thiadiazole-sulfonamide fragment in the molecule of CA inhibitors (CAIs) drastically affects both inhibition efficacy and binding within the enzyme active site, as rationalized by means of X-ray crystallography of the adduct of hCA II with 4-(1-adamantylcarboxamidomethyl)benzenesulfonamide. Comparing the present X-ray structure with that of the corresponding 1,3,4-thiadiazole-sulfonamide compound possessing the 1-adamantylcarboxamide moiety, important differences of binding emerged, which explain the highly different inhibition profile of the two compounds against the investigated CA isoforms, most of which (CA I, II, IX and XII) are important drug targets.